Intratumoral CD103+ CD8+ T cells predict response to PD-L1 blockade

<jats:sec> <jats:title>Background</jats:title> <jats:p>CD8+ tissue-resident memory T (T<jats:sub>RM</jats:sub>) cells, marked by CD103 (<jats:italic>ITGAE</jats:italic>) expression, are thought to actively suppress cancer progression, leading to the hypothesis that their presence in tumors may predict response to immunotherapy.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>Here, we test this by combining high-dimensional single-cell modalities with bulk tumor transcriptomics from 1868 patients enrolled in lung and bladder cancer clinical trials of atezolizumab (anti-programmed cell death ligand 1 (PD-L1)).</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p> <jats:italic>ITGAE</jats:italic> was identified as the most significantly upregulated gene in inflamed tumors. Tumor CD103+ CD8+ T<jats:sub>RM</jats:sub> cells exhibited a complex phenotype defined by the expression of checkpoint regulators, cytotoxic proteins, and increased clonal expansion.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Our analyses indeed demonstrate that the presence of CD103+ CD8+ T<jats:sub>RM</jats:sub> cells, quantified by tracking intratumoral CD103 expression, can predict treatment outcome, suggesting that patients who respond to PD-1/PD-L1 blockade are those who exhibit an ongoing antitumor T-cell response.</jats:p> </jats:sec>